This paper is concerned with the effects of the axle misalignment of a truck with independently rotating wheels (IRWs) on the wheel lateral force and flange wear. Since a truck with IRWs lacks self-steering ability, it is of concern that the wheel flange remains in contact with the rail owing to the effect of axle misalignment in parallelity, resulting in rapid wear of the flange upon continuous contact with the rail. Numerical simulations are carried out using an analytical vehicle model with axle misalignment. The obtained results are as follows. Even if misalignment is small, a vehicle with IRWs tends to run under the flange contact condition, and thus a continuous lateral force acts between the flange and rail. A vehicle with IRWs that has axle misalignment only in the lateral direction does not tend to run with continuous flange contact. In the range of misalignment in parallelity considered in this paper, the wheel lateral force increases with increasing misalignment, and the wheel lateral force acting on the IRWs increases more rapidly than that acting on the solid wheelset. The wheel lateral force generated by misalignment is equivalent to that generated during the negotiation of a curved track with a certain radius, which causes the attack angle to correspond to the angle of misalignment.